This document provides a comprehensive overview of nerve and membrane potentials, including the classification and properties of nerve fibers, the ionic basis of resting and action potentials, and the physiological processes involved in nerve excitability. It discusses the structure of neurons, the dynamics of action potential propagation, the role of ion channels, and the influence of electrolyte imbalances on nerve function. Additionally, it outlines the implications of hyperkalemia and hypokalemia on muscle and cardiac activity.

1. Nerve and
Membrane Potential
Prof. Vajira Weerasinghe
Senior Professor of Physiology
Department of Physiology, Faculty of Medicine,
University of Peradeniya and Consultant Neurophysiologist,
Teaching Hospital Peradeniya
www.slideshare.net/vajira54

2. ILO
• Describe the Classification of nerve fibers: based on structure,
diameter and functions.
• Describe the Properties of nerve fibers and basic structure of a
nerve cell
• Describe the Ionic basis for resting membrane potential
• Describe Ionic basis for action potential.
• Explain the Alteration in excitability in electrolyte imbalance

3. Learning resources
• Textbooks
– Ganong 26th edition
– Guyton
– Netter's Atlas of Neuroscience
• Web resources
• .edu
• .ac.uk
• .ac.lk
• www.slideshare.net

4. Excitable Cells
• Basic cell of the nervous system is nerve cell
• Nerve cell or neuron is an excitable cell
• Excitable cells are capable of generation and
transmission of electrochemical impulses along the
membrane
• Muscle cells are also excitable cells
Nerve cell or neuron Muscle cell

5. Excitable cells
Excitable Non-excitable
Red cell
GIT
neuron
muscle
•RBC
•Intestinal cells
•Fibroblasts
•Adipocytes
•Nerve
•Muscle
•Skeletal
•Cardiac
•Smooth

6. Basic structure of a neuron
• Cell body contains the nucleus
• Dendrites extend outward from the cell body and arborize
extensively to aid their role in receiving incoming signals,
processing the information, and then transmitting the
information to the cell body
• Axon originates from a thickened area of the cell body called
axon hillock
• First portion of the axon is called the initial segment
• Axon divides into presynaptic terminals ending in a number of
synaptic knobs that are also called terminal buttons or boutons

7. Neuron - functional aspect
• From a functional point of view, neurons generally
have four important zones:
• (1) a dendritic zone where multiple local potential
changes generated by synaptic connections are
integrated
• (2) a site where propagated action potentials are
generated (initial node of Ranvier)
• (3) an axonal process that transmits propagated
impulses to the nerve endings;
• (4) the nerve endings, where action potentials cause
the release of synaptic transmitters.

8. Neuron – myelin sheath
• Axons acquire a myelin sheath, a protein–lipid complex that is
wrapped around the axon
• Myelin forms from Schwann cells in the peripheral nervous
system or oligodendrocyte in the CNS
• Myelin sheath envelops the axon except at the nodes of
Ranvier, periodic 1-µm gaps where the axon is unmyelinated
• Myelinated axons are faster in conducting electrical impulses
– eg. Conduction velocity of unmyelinated axons 1-2 m/s whereas it is 50-
100 m/s in myelinated axons

9. Classification of nerve fibre types

10. Classification of nerve fibre types

11. Membrane potential
• A potential difference exists across all cell
membranes
• This is called
– Resting Membrane Potential (RMP)

12. Membrane potential
– Inside is negative with respect to the outside
– This is measured using microelectrodes and
oscilloscope
– This is about -70 to -90 mV

13. Excitable tissues
• Excitable tissues have more
negative RMP
( - 70 mV to - 90 mV)
excitable Non-excitable
Red cell
GIT
neuron
muscle
• Non-excitable tissues
have less negative RMP
-53 mV epithelial cells
-8.4 mV RBC
-20 to -30 mV fibroblasts
-58 mV adipocytes

14. Resting Membrane Potential
• This depends on following factors
– Ionic distribution across the membrane
– Membrane permeability
– Other factors
• Na+/K+ pump

15. Ionic distribution
• Major ions
– Extracellular ions
• Sodium, Chloride
– Intracellular ions
• Potassium, Proteinate
K+
Pr-
Na+ Cl-

16. Ionic distribution
Ion Intracellular Extracellular
Na+
10 142
K+
140 4
Cl-
4 103
Ca2+ 0 2.4
HCO3
- 10 28

17. Gibbs Donnan Equilibrium
• When two solutions
containing ions are
separated by membrane
that is permeable to some
of the ions and not to others
an electrochemical
equilibrium is established
• Electrical and chemical
energies on either side of
the membrane are equal
and opposite to each other

18. Flow of Potassium
• Potassium concentration intracellular is more
• Membrane is freely permeable to K+
• There is an efflux of K+
K+
K+
K+
K+
K+ K+
K+
K+
K+
K+

19. Flow of Potassium
• Entry of positive ions in to the extracellular fluid
creates positivity outside and negativity inside
K+
K+
K+
K+
K+ K+
K+
K+
K+
K+

20. Flow of Potassium
• Outside positivity resists efflux of K+
• (since K+ is a positive ion)
• At a certain voltage an equilibrium is reached
and K+ efflux stops
K+
K+
K+
K+
K+ K+
K+
K+
K+
K+

21. Nernst potential (Equilibrium potential)
• The potential level across the membrane that
will exactly prevent net diffusion of an ion
• Nernst equation determines this potential

22. Nernst potential (Equilibrium potential)
• The potential level across the membrane that
will exactly prevent net diffusion of an ion
Ion Intracellular Extracellular Nernst
potential
Na+
10 142 +60
K+
140 4 -90
Cl-
4 103 -89
Ca2+ 0 2.4 +129
HCO3
- 10 28 -23
(mmol/l)

23. Goldman Equation
• When the membrane is permeable to several ions the
equilibrium potential that develops depends on
– Polarity of each ion
– Membrane permeability
– Ionic conc
• This is calculated using Goldman Equation (or GHK
Equation)
• In the resting state
– K+ permeability is 20 times more than that of Na+

24. Ionic channels
• Leaky channels (leak channels)
– Allow free flow of ions
– K+ channels (large number)
– Na+ channels (fewer in number)
– Therefore membrane is more permeable to K+

25. Na/K pump
• Active transport system for Na+-K+
exchange using energy
• It is an electrogenic pump since 3 Na+
efflux coupled with 2 K+ influx
• Net effect of causing negative charge
inside the membrane
3 Na+
2 K+
ATP ADP

26. Factors contributing to RMP
• One of the main factors is K+ efflux which causes
negativity inside the membrane
– Nernst Equilibrium Potential: -94mV
– K+ efflux through leak channels
– There are more K+ leak channels than Na+ leak channels
– Na+ permeability is only 5% (20 times) that of K+
• Na+/K+ pump causes more negativity inside the
membrane
– 3 Na+ removed (leaving 3 negatives inside) with 2 K+
replaced (2 negatives become zero), excess negativity
inside
• Negatively charged protein remaining inside due
to impermeability contributes to the negativity
inside the membrane
• Contribution of Na+ influx is little
– Nernst Equilibrium Potential: +61mV
– Causes less negativity inside the membrane
• Net result: -70 mV inside

27. Electrochemical gradient
• At this electrochemical equilibrium, there is an exact
balance between two opposing forces:
• Chemical driving force = ratio of concentrations on 2
sides of membrane (concentration gradient)
• The concentration gradient that causes K+ to move from inside to
outside taking along positive charge and
• Electrical driving force = potential difference across
membrane
• opposing electrical gradient that increasingly tends to stop K+ from
moving across the membrane
• Equilibrium: when chemical driving force is balanced
by electrical driving force

28. Action potential

29. Action Potential (A.P.)
• When an impulse is generated
– Inside becomes positive
– Causes depolarisation
– Nerve impulses are transmitted as AP

30. -70
+30
RMP
Hyperpolarisation

31. Inside of the membrane is
• Negative
– During RMP
• Positive
– When an AP is generated
-70
+30

32. • Initially membrane is slowly depolarised
• Until the threshold level is reached
– (This may be caused by the stimulus)
-70
+30
Threshold level

33. • Then a sudden
change in polarisation
causes sharp
upstroke
(depolarisation) which
goes beyond the zero
level up to +35 mV
-70
+30

34. • Then a sudden
decrease in
polarisation causes
initial sharp down
stroke (repolarisation)
-70
+30

35. • When reaching the
Resting level rate
slows down
• Can go beyond the
resting level
– hyperpolarisation
-70
+30

36. • Spike potential
– Sharp upstroke and
downstroke
• Time duration of AP
– 1 msec
-70
+30
1 msec

37. All or none law
• Until the threshold level the potential is graded
• Once the threshold level is reached
– AP is set off and no one can stop it !
– Like a gun

38. All or none law
• The principle that the strength by which a nerve
or muscle fiber responds to a stimulus is not
dependent on the strength of the stimulus
• If the stimulus is any strength above threshold,
the nerve or muscle fiber will give a complete
response or otherwise no response at all

39. Physiological basis of AP
• When the threshold level is reached
– Voltage-gated Na+ channels open up
– Since Na conc outside is more than the inside
– Na influx will occur
– Positive ion coming inside increases the positivity of the
membrane potential and causes depolarisation
– When it reaches +30, Na+ channels closes
– Then Voltage-gated K+ channels open up
– K+ efflux occurs
– Positive ion leaving the inside causes more negativity inside
the membrane
– Repolarisation occurs

40. Physiological basis of AP
• Since Na+ has come in and K+ has gone out
• Membrane has become negative
• But ionic distribution has become unequal
• Na+/K+ pump restores Na+ and K+ conc slowly
– By pumping 3 Na+ ions outward and 2+ K ions
inward

41. VOLTAGE-GATED ION CHANNELS
• Na+ channel
– This has two gates
• Activation and inactivation gates
outside
inside
Activation gate
Inactivation gate

42. • At rest: the activation gate is closed
• At threshold level: activation gate opens
– Na+ influx will occur
– Na+ permeability increases to 500 fold
• when reaching +30, inactivation gate closes
– Na influx stops
• Inactivation gate will not reopen until resting membrane potential is reached
• Na+ channel opens fast
outside
inside
outside
inside
-70 Threshold level +30
Na+ Na+
outside
inside
Na+
m gate
h gate

43. VOLTAGE-GATED K+ Channel
• K+ channel
– This has only one gate
outside
inside

44. – At rest: K+ channel is closed
– At +30
• K+ channel open up slowly
• This slow activation causes K efflux
– After reaching the resting still slow K+ channels
may remain open: causing further hyperpolarisation
outside
inside
outside
inside
-70 At +30
K+ K+
n gate

45. Summary

46. Refractory Period
• Absolute refractory
period
– During this period nerve
membrane cannot be
excited again
– Because of the closure
of inactivation gate
-70
+30
outside
inside

47. Refractory Period
• Relative refractory
period
– During this period nerve
membrane can be
excited by supra
threshold stimuli
– At the end of
repolarisation phase
inactivation gate opens
and activation gate
closes
– This can be opened by
greater stimuli strength
-70
+30
outside
inside

48. Propagation of AP
• When one area is depolarised
• A potential difference exists between that site
and the adjacent membrane
• A local current flow is initiated
• Local circuit is completed by extra cellular fluid

49. Propagation of AP
• This local current flow will cause opening of
voltage-gated Na channel in the adjacent
membrane
• Na influx will occur
• Membrane is deloparised

50. Propagation of AP
• Then the previous area become repolarised
• This process continue to work
• Resulting in propagation of AP

51. Propagation of AP

52. Propagation of AP

53. Propagation of AP

54. Propagation of AP

55. Propagation of AP

56. Propagation of AP

57. Propagation of AP

58. Propagation of AP

59. AP propagation along myelinated
nerves
• Na channels are conc
around nodes
• Therefore depolarisation
mainly occurs at nodes

60. AP propagation along myelinated
nerves
• Local current will flow one node to another
• Thus propagation of A.P. is faster. Conduction
through myelinated fibres also faster.
• Known as Saltatory Conduction

63. • Re-establishment of Na & K conc after A.P.
– Na-K Pump is responsible for this.
– Energy is consumed
3 Na+
2 K+
ATP ADP

64. Muscle action potentials
• Skeletal muscle
• Smooth muscle
• Cardiac muscle

65. Skeletal muscle
• Similar to nerve action potential

66. Cardiac muscle action potential
Phases
• 0: depolarisation
• 1: short repolarisation
• 2: plateau phase
• 3: repolarisation
• 4: resting
Duration is about 250 msec

67. Cardiac muscle action potential
Phases
• 0: depolarisation
(Na+ influx through fast Na+
channels)
• 1: short repolarisation
(K+ efflux through K+
channels, Cl- influx as well)
• 2: plateau phase
(Ca++ influx through slow
Ca++ channels)
• 3: repolarisation
(K+ efflux through K+
channels)
• 4: resting

68. Smooth muscle
• Resting membrane potential may be about -55mV
• Action potential is similar to nerve AP
• But AP is not necessary for its contraction
• Smooth muscle contraction can occur by hormones

69. Applied physiology
• Decreasing the external Na+ concentration reduces the size of the
action potential but has little effect on the resting membrane potential
• If the extracellular level of K+ is increased (hyperkalemia),the resting
potential moves closer to the threshold for eliciting an action
potential, thus the neuron becomes more excitable
• This may inactivate Na+ channels, which increases refractory period
and may lead to cardiac arrhythmias
• If the extracellular level of K+ is decreased (hypokalemia),the
membrane potential is reduced and the neuron is hyperpolarized
• This may lead to delayed ventricular repolarisation which can
contribute to cardiac arrhythmias
• Major electrolyte abnormalities can lead to skeletal muscle spasms
and seizures

70. Hyperkalemia
• Causes
– Advanced renal failure
– Adrenal insufficiency
– Distal renal tubular acidosis
– Type 1 diabetes
– Dehydration
– Angiotensin II receptor blocker use
– Angiotensin-converting enzyme (ACE) inhibitor use
– Non-steroidal anti-inflammatory drugs(NSAIDs) use
– Potassium sparing diuretics
• Symptoms include
– Muscle pain
– Muscle weakness
– Numbness
– Cardiac arrhythmias
– Nausea
– Extremely high levels of plasma K+ can lead to cardiac arrest and death

71. Hypokalaemia
• Causes
– Diuretics
– Diabetic ketoacidosis
– Renal tubular acidosis
– Genetic conditions
• Symptoms
– Muscle weakness
– Fatigue
– Constipation
– Muscle cramping
– Palpitations
– Psychological symptoms (depression or psychosis)
– Severe hypokalemia may lead to problems with cardiac rhythmicity and can
manifest as bradycardia, tachycardia, premature beats, atrial or ventricular
fibrillation